Seizures are defined as the transient physiological disorders of the brain, which occur due to aberrant and abnormal electrical discharges in a group of cortical neurons (1). Seizures impose a significant burden on the patients and healthcare system, accounting for 1.2% of the referrals to the emergency department (ED), with 24% of these cases often confirmed as first-time seizures (2). Epileptic seizures are another common cause of referral to the ED. Several studies have indicated that approximately 45% of new-onset seizures (NOSs) have no known etiology, and 40-50% of these patients eventually receive an epilepsy diagnosis in their ED consultation (3). Although the exact etiology of epileptic seizures remains unclear, dominant MRI findings have shown the presence of T2-hyperintense lesions in the subcortical and periventricular white matter, particularly in the external capsule and anterior temporal lobes, often involving these centers compared to the scattered forms of cerebral small vessel diseases (4).
Neurologists are often concerned that the incidence of NOSs could be the primary sign of chronic epilepsy or non-epileptic events, such as syncope, transient ischemic attacks, and psychogenic non-epileptic seizures. Another issue in this regard for physicians is the cause of the seizure, which may either be direct, in which case the elimination of this contributing factor prevents seizure recurrence, or there may be an unidentified seizure with the risk of recurrence (approximately 40%) within two years (5-8).
Continuous electroencephalography (cEEG) monitoring is an effective diagnostic tool for the detection of seizures and other disorders in patients with critical conditions. The periodic and rhythmic patterns that are often observed in these patients are associated with seizures in some cases (9-16). Early EEG has been reported to exhibit higher efficacy in epilepsy (51%) compared to delayed EEG (34%) (17). Conflicting findings have been proposed regarding the minimum time required for EEG. EEG is considered crucial due to the thermal management protocols that are used for seizure relaxation, which may conceal the clinical symptoms of seizure activity, only providing electrical diagnosis. Moreover, EEG could be effective in the differential diagnosis of seizure activity from shivering to other non-epileptic movements (18, 19).
To date, no EEG studies have been performed on the patients referring to the ED with the first seizure. The present study aimed to investigate the EEG findings in the patients with the first seizure referring to the ED of Ghaem Hospital in Mashhad, Iran in order for the rapid diagnosis of epilepsy, reducing the associated complications, and provide timely and effective treatment for these patients.
This cross-sectional study was conducted on the patients with the first seizure referring to the ED of Ghaem Hospital in Mashhad, Iran in January 2018. Before sampling, the study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1397.008). The research objectives and methodology were explained to the patients and their caregivers, and written informed consent was obtained prior to enrollment.
The participants were selected via convenience sampling, and eligible patients were enrolled in the study until achieving the required sample size. The inclusion criteria were age of more than 17 years, first seizure attack, and providing written informed consent to participate. The exclusion criteria were the cases in which seizure diagnosis was not confirmed by a neurologist (e.g., pseudoseizure, seizure during pregnancy, and febrile seizures), history of using seizure-inducing medications, and presence of metabolic disorders as reported in the medication history and tests of the patients.
After stabilizing the conditions of the patients, data were collected using a demographic form containing data on age, gender, and comorbidities, which was completed by the researcher. Following that, EEG was performed on the patients in the ED within 24 hours after the first attack. Changes in the EEG were examined by two neurologists, and antiepileptic medications were prescribed to the patients based on the EEG findings (epileptic changes). Finally, the frequency of pathological changes in the EEG findings was determined in the patients.
Data analysis was performed in SPSS version 18 using descriptive statistics (measures of central tendency and dispersion, frequency distribution) in the form of tables and charts. In the intergroup comparison of quantitative variables (e.g., genders), independent t-test was used for the data with normal distribution, and Mann-Whitney U test was utilized for the data with non-normal distribution. In addition, the intergroup comparison of qualitative variables (e.g., genders) was carried out using Chi-square and Fisher’s exact test if necessary. In all the statistical analyses, the significance level was considered to be 0.05.
In total, the sample population consisted of 35 male patients (43.8%) and 45 female patients (56.2%) (Table 1).
Among the studied patients, five cases (6.3%) were aged ≤20 years, 18 cases (22.5%) were aged 21-40 years, 27 cases (33.8%) were aged 41-60 years, 23 cases (28.8%) were aged 61-80 years, and seven cases (8.8%) were aged ≥81 years. It is notable that the minimum and maximum age of the patients were 18 and 90 years, respectively. The mean age of the patients was 52.54±19.33 years (median: 53 years).
In terms of education level, 58 patients (72.5%) had secondary education, and 22 cases (27.5%) had higher education levels than high school. No family history of seizures was reported in 75 patients (93.8%), while five cases (6.2%) had a family history of seizures. On the same note, 67 patients (83.8%) had no disease history, while six cases (7.5%) had a history of diabetes, three cases (3.8%) had a history of hypertension, and four patients (5%) had a history of stroke (Table 2).
According to the results, 68 patients (85%) were referred to the ED by family members, and 12 cases (15%) were referred by emergency medical services to the ED of Ghaem Hospital in Mashhad. The other findings indicated that 71 patients (88.8%) were non-smokers, while nine cases (11.2%) were smokers. In addition, 46 patients (57.5%) had normal EEG findings with no epileptic discharge, whereas 34 cases (42.5%) had abnormal EEG findings (pathological with epileptic discharge) (Table 3).
In the present study, Pearson’s Chi-squared test was used to examine the correlation between the EEG findings and gender of the patients referring to the ED of the hospital, and the obtained results indicated no significant correlation between the gender of the patients and their EEG findings (χ2=0.159; df=1; P>0.05) (Tables 4 & 5).
Moreover, Yates’ continuity correction yielded a similar result in this regard. Therefore, it could be concluded that the ratio of the normal and pathological EEG findings had no significant difference between the male and female patients.
Pearson’s chi-squared test was also used to examine the correlation between the EEG findings and age of the patients referring to the ED of the hospital, and the obtained results showed no significant correlation between the age of the patients and their EEG findings (χ2=2.456; df=4; P>0.05). Therefore, it could be concluded that the ratio of the normal and pathological EEG findings had no significant difference between the patients in various age ranges.
In the current research, Pearson’s chi-squared test was employed to examine the correlation between the EEG findings and family history of epilepsy in the patients referring to the ED of the hospital, and the obtained results demonstrated no significant correlation between the family history of epilepsy in the patients and their EEG findings (χ2=0.668; df=1; P>0.05). Furthermore, Yates’ continuity correction yielded a similar result in this regard. Therefore, it could be concluded that the ratio of the normal and pathological EEG findings had no significant difference between the patients with and without the family history of epilepsy (Tables 6 & 7).
Pearson’s chi-squared test was also used to assess the correlation between the EEG findings and medical disease history of the patients referring to the ED of the hospital, and the obtained results indicated no significant correlation between the history of medical diseases and EEG findings (χ2=0.953; df=3; P>0.05). Therefore, it could be concluded that the ratio of the normal and pathological EEG findings had no significant difference between the patients with variable medical records (Tables 8 & 9).
The first seizure is an unexpected, horrifying event to the patient, as well as the observers and family members. The detection of seizures is common in routine clinical practice. Statistics suggest that a minimum of 4% of the general population experience one or more nonfebrile seizures in their lifetime (20,21). The sensitivity of conventional EEG in seizure detection has been estimated at 25-56%, and its specificity has been reported to be 70-90% (22). The present study aimed to investigate the EEG findings in the patients with the first seizure referring to the ED of Ghaem Hospital in Mashhad (Iran) so as to enable the rapid diagnosis of epilepsy, reduce the associated complications, and provide rapid and effective treatment. This cross-sectional study was conducted on 80 patients with the first seizure, including 35 males (43.8%) and 45 females (56.2%). The mean age of the patients was 52.54±19.33 years. Overall, 46 patients (57.5%) had normal EEG findings, while 34 cases (42.5%) had abnormal (pathological) EEG findings.
In a prospective study in this regard, Paliwal et al. (2015) examined all the patients who were diagnosed with the first seizure referring to the hospital during 2008-2011. In the mentioned research, early EEG was carried out at the ED before discharge, and specialized examinations were also performed by a neurologist within the first two weeks. In addition, a neurologist was responsible for the clinical decision-making. Seizure recurrence was evaluated within a follow-up period of nine months to three years. Among 136 studied patients, 92 were male and 44 were female, and the mean age of the patients was 32 years (range: 16-73 years). According to the obtained results, 40 patients had abnormal EEG, and the patients with abnormal EEG (51% versus 11%) and abnormal MRI (53% versus 28%) were more likely to be allocated to the medication therapy group. Furthermore, the findings of the study indicated that abnormal MRI was independently associated with the higher risk of recurrence, and EEG contributed to the medical decision-making in the patients with abnormal MRI (23). In the present study, 42.5% of the patients were observed to have abnormal EEG findings.
Wyman et al. (2016) conducted a first-time seizure ED EEG study on 71 patients receiving EEG. In the mentioned study, all the EEGs were performed within 11 hours following the seizure (average: 3.85 hours). In addition, 24% of the patients (95% confidence interval of 15-36%) were diagnosed with epilepsy and prescribed with antiepileptic medications at the ED. Among 34 patients who were followed-up by an epileptologist, nine cases were diagnosed with epilepsy at the ED, and none of these patients discontinued their antiepileptic medication in their initial follow-up. Finally, it was concluded that the EEG function at the ED in the adults who had the first seizure yielded significant results for the epilepsy diagnosis, which also contributed to the immediate onset of antiepileptic medication (24).
In the current research, 34 patients (42.5%) referring to the ED had abnormal (pathological) EEG findings. In a prospective study entitled “EEG as Part of the Decision-making Process in the Emergency Department”, Yigit et al. (2013) examined 110 patients with seizure or seizure-mimicking symptoms, and EEG was reported to be normal in 56% of the patients with the first seizure (25).
In the present study, 57.5% of the patients had normal EEG findings, and the positive predictive value of EEG was observed to be higher than 80% after the first seizure. It has been well documented that the detection of abnormal signs in EEG is associated with the increased risk of seizure recurrence (26). In a research in this regard, King et al. evaluated the detection of epilepsy based on first-time seizure reports in 300 patients with seizure, and generalized or focal epilepsy syndrome was clinically diagnosed in 141 cases (47%). Moreover, the EEG findings resulted in the diagnosis of epilepsy syndrome in 232 patients (77%). The EEGs were observed to be more effective in the detection of epilepsy within 24 hours after the diagnosis of epilepsy as opposed to later EEGs (51% versus 34%) (17).
In the present study, EEG was obtained within 24 hours after the first seizure at the ED, which was reported to be pathological in 42.5% of the studied patients.
In this regard, Schreiner et al. conducted a prospective study on 157 patients with unknown first-time seizures, reporting that seizures were observed in 13.3% of the EEG cases without the diagnosis of various types of epilepsy (27). Therefore, it must be borne in mind that normal EEGs might also be associated with errors, and continuous follow-up of the patient and using a combination of imaging tools could predispose the diagnosis of epilepsy.
Based on the results of the present study and correlations between the outcomes and history of the risk factors for epilepsy (based on the EEG findings), it could be inferred that the ratio of normal and pathological EEG findings had no significant difference in terms of the demographic data of the patients (age, gender, family history of epilepsy, smoking habits, medical disease history, and mode of referral to the ED). Nevertheless, some studies have denoted that positive family history may increase the risk of epilepsy 2-3 times (28,29). For instance, Bhalla et al. stated that family history is a key risk factor for focal epilepsy (30). Furthermore, Ottman et al. reported that the risk of seizure increases in the individuals with the family history of seizures (31), while no significant associations were observed between the family history of epilepsy and normal and pathological EEG findings in the current research.
Limitations of the Study and Research Implications
The main limitations of the study were the small sample size and lack of patient follow-up. Therefore, it is recommended that similar investigations be conducted on larger sample sizes, and patient follow-up is also suggested in the next steps.
According to the results, 42.5% of the patients with the first seizure had abnormal (pathological) EEG findings. However, it seems that the accurate examination of these patients may require the use of other diagnostic tools along with EEG in order to achieve the definitive diagnosis of epilepsy and seizure.
This study was derived from thesis of Mohammadreza shirzadeh registered in Mashhad University of Medical Sciences (960494). The authors would like to thank and appreciate the material aid and spiritual support of the Research Deputy of Mashhad University of Medical Sciences and the patients participating in the project. We also thank the Clinical Research Development Unit of Peymanieh Educational and Research and Therapeutic Center of Jahrom University of Medical Sciences for revising the manuscript.
Conflict of Interest
The authors declare no conflict of interest.